NM_015268.4:c.69-2119G>T

Variant names:

• chr3-132444356-G-T
• rs17404153
• NM_015268.4:c.69-2119G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015268.4(DNAJC13):​c.69-2119G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,200 control chromosomes in the GnomAD database, including 1,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1030 hom., cov: 32)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 51 publications found

Genes affected

DNAJC13 (HGNC:30343): (DnaJ heat shock protein family (Hsp40) member C13) This gene encodes a member of the Dnaj protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. The encoded protein associates with the heat-shock protein Hsc70 and plays a role in clathrin-mediated endocytosis. It may also be involved in post-endocytic transport mechanisms via its associations with other proteins, including the sorting nexin SNX1. Mutations in this gene are associated with Parkinson's disease. [provided by RefSeq, Jun 2016]

DNAJC13 Gene-Disease associations (from GenCC):

• hereditary late onset Parkinson disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.69-2119G>T		intron_variant	Intron 2 of 55	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.69-2119G>T		intron_variant	Intron 2 of 56		NP_001316055.1
DNAJC13	XM_047447819.1	c.69-2119G>T		intron_variant	Intron 2 of 56		XP_047303775.1
DNAJC13	XM_047447820.1	c.69-2119G>T		intron_variant	Intron 2 of 55		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.69-2119G>T		intron_variant	Intron 2 of 55	1	NM_015268.4	ENSP00000260818.6
DNAJC13	ENST00000486798.5	n.134-2119G>T		intron_variant	Intron 2 of 19	1
DNAJC13	ENST00000650455.1	n.69-2119G>T		intron_variant	Intron 2 of 56			ENSP00000496825.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15954 AN: 152082 Hom.: 1030 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15959 AN: 152200 Hom.: 1030 Cov.: 32 AF XY: 0.110 AC XY: 8200 AN XY: 74406

African (AFR) AF: 0.0272 AC: 1128 AN: 41544

American (AMR) AF: 0.130 AC: 1988 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3472

East Asian (EAS) AF: 0.129 AC: 670 AN: 5180

South Asian (SAS) AF: 0.165 AC: 798 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2057 AN: 10568

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8475 AN: 68006

Other (OTH) AF: 0.112 AC: 235 AN: 2102

Alfa AF: 0.119 Hom.: 3341

Bravo AF: 0.0960

Asia WGS AF: 0.136 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.58
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17404153; hg19: chr3-132163200;